Alcoholic hepatitis is a serious consequence of excessive alcohol consumption and may result in death during the active stages of the disease or in the later development of cirrhosis. We are investigating the effects of prednisolone or d-penicillamine versus placebo therapy in patients with alcoholic hepatitis to determine if such therapy influences early mortality, rate of resolution of liver function test abnormalities, incidence of complications (bleeding, hepatic coma, infection, renal failure) and the histologic features of alcoholic hepatitis. The studies are performed in randomized double-blind 28-32 day trials. In addition, all patients have determination before and after the study of the wedged hepatic venous pressure and inferior vena cava pressure as an index of portal hypertension; BSP storage and maximal excretory capacity; and plasma volume (125I-labelled albumin). In those patients in whom liver biopsy is possible, hepatic collagen proline hydroxylase activity and urinary hydroxyproline excretion are measured as indices of fibrogenesis. In the studies with d-penicillamine, hepatic copper concentration is determined. From the results of our initial Study I (prednisolone versus placebo), it is suggested that survival is improved by corticosteroid therapy in severely ill patients who have marked prolongation of the prothrombin time and increased serum bilirubin at the onset. A further trial of prednisolone versus placebo therapy in high risk patients defined by a discriminant analysis function is underway. Additional investigations will include determination of the distribution and relative amounts of collagen Types I and III by immunofluorescent methods and study of indocyanine green (ICG) disappearance as an additional measure of hepatic cell function and liver blood flow. Further studies include determination of renin, angiotensin II, and aldosterone in peripheral and hepatic venous blood to assess both peripheral blood levels and the efficiency of hepatic extraction before and after therapy. Studies of amino acid patterns and vitamin B6 and ascorbic acid metabolism are also underway.